clinical research programs dept. of microbiology … in clinical... · clinical research programs...

M.Sc. in Clinical Research

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CLINICAL RESEARCH PROGRAMS

DEPT. OF MICROBIOLOGY

SCHOOL OF SCIENCES

GUJARAT UNIVERSITY


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Course Outline

Semester I

Module I MSCCR101 Elements of Microbiology & Biotechnology

70 hrs

Module II MSCCR102 Fundamentals of Anatomy, Physiology & Pathophysiology

70 hrs

Module III MSCCR103 General Pharmacology, Pharmacokinetics & Pharmacodynamics of Drugs

70 hrs

Semester II

Module IV

MSCCR201 Pharma-Medicine & Clinical Research

70 hrs

Module V MSCCR202 Regulations in Clinical Research 70 hrs

Module VI

MSCCR203 Clinical Research Operations Management

70 hrs

Semester III

Module VII

MSCCR301 Conduct of Bioequivalence Studies 70 hrs

Module VIII

MSCCR302 Clinical Data Management & Biostatistics

70 hrs

Module IX

MSCCR303 Pharmacovigilance & Post Marketing Surveillance

70 hrs

Semester IV- MSCCR401 Dissertation


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SEMESTER I MODULE I: ELEMENTS OF MICROBIOLOGY & BIOTECHNOLOGY 70 hrs

Basic Microbiology

• Science of Microbiology

• Structure of prokaryotic cell, virus

• Methods in Microbiology-viewing, measuring, culturing and preservation of

microorganisms

• Growth of microbes

� Growth type / rate / phases

� Nutrients for microbes and their transfer

• Control of microorganisms

� Death rate, sterilization

� Physical controls

� Chemical controls

Basic Biotechnology

• Introduction to bacterial genetics and rDNA technology

o DNA, RNA, protein composition and structure

o Transcription and translation

o Gene regulation

o Introduction, and molecular biology tools for rDNA technology

o Methods of gene transfer and plasmid technology

o Guidelines for genetic engineering

• Basic techniques in rDNA technology PAGE, DNA isolation and purification, blotting

techniques, PCR, nucleic acid sequencing

• Introduction to animal biotechnology - transgenic animals

• Biotechnology derived drugs and their processes


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Clinical microbiology

• Host parasite interaction

� Microorganisms and human diseases - properties and capacities of

selected pathogens

� Basic aspect of immune systems

� Diagnostic immunology

� Prevention of microbial diseases – an overview

Quality control and assurance

• Biotechnology - society, risks, ethics, patenting

• Biosafety guidelines

• Role of culture collection centres, public health laboratories and regulatory agencies

• National accreditation board for laboratories

• Bioethics principles, international codes and guidelines in India

• Role of regulatory bodies involved in testing and approval of biotechnology derived

drugs


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MODULE II: FUNDAMENTALS OF ANATOMY, PHYSIOLOGY &

PATHOPHYSIOLOGY 70 hrs

• Basics of Anatomy & Physiology: Cells, tissues, structure and functions

• Blood: Plasma, erythrocytes, hemoglobin and anemia, leucocytes, thrombocytes,

coagulation of blood, blood groups and transfusion, immunity and tissue macrophage

system and lymph.

• Nerve: Nerve biophysics, Neuron, Nerve conduction and classification of nerve fibers

• Muscle: Skeletal muscle structure and mechanism of contraction, Mechanism of muscle

contraction and Neuromuscular transmission.

• Cardiovascular System: Anatomy of the heart, Circulatory system including Arterial

and Venous system with special reference to the names and positions of main arteries and

veins, Properties of Cardiac muscle, Blood pressure and its regulation, Renin Angiotensin

system and its significance, Physiology of cardiac muscle, cardiac impulse,

electrocardiogram, cardiac cycle, heart sounds, heart rate and its regulation, cardiac

output, arterial pulse and venous pulse, cardiovascular changes in muscular exercise,

circulatory shock and cardiac failure.

• Respiratory System: Anatomy of Respiratory organs, Functional anatomy of respiratory

system, mechanics of respiration, lung volumes and capacities, dead space, alveolar

ventilation and diffusion of gases, parameters like Vital Capacity, Total Capacity and

Forced Expiratory Volume, transport of oxygen, transport of carbon dioxide, regulation

of respiration and artificial respiration.

• Excretory System and Body Fluids: Various parts of urinary system and their functions,

Structure and functions of Nephron, formation of urine, micturition, renal function tests,

electrolyte balance, juxtaglomerualr apparatus, body fluids, skin and body temperature,

metabolic function of liver, gall bladder and related glands, mechanisms of excretion

• Endocrine Glands and Reproduction: Role of Endocrine Glands in Regulation and

Integration of various functions of the Body, Anatomy and Physiology, General

considerations, pituitary gland, thyroid gland, endocrine regulation of calcium and


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phosphorus metabolism, parathyroid gland, islets of langerhans, adrenal gland,

prostaglandins, thymus and pineal gland, female reproductive system, male reproductive

system

• Nervous System: Divisions of Nervous System, Central Nervous System (Brain &

Spinal Cord), Reflex action, Electroencephalogram (EEG), Overview of

Neurotransmitters, Peripheral Nervous System (PNS) (Cranial nerves & spinal

nerves)Synaptic transmission, sensory receptors, pain, reflex action, spinal cord,

thalamus, cerebellum, cerebral cortex, Sleep, hypothalamus, cerebrospinal fluid,

autonomic nervous system

• Digestive System: Organization of digestive tract, digestive secretions, gastrointestinal

hormones, liver, gastrointestinal motility, absorption of food

• Special Senses: Vision, hearing, chemical senses

• Fundamentals of Pathophysiology: Derangement of Homeostasis and hemodynamics,

Definition, terminology, pathology of following diseases including etiology, risk factors,

signs and symptoms, overview of treatment and diagnosis of the disease

• Diseases- Systemic pathology of blood vessels and lymphatics, liver, exocrine pancreas,

kidney, endocrine system, musculoskeletal system, nervous system, system associated

diseases like Hypertension, congestive heart failure, cardiac arrhythmias, ischemic heart

diseases, obesity, atherosclerosis, bronchial asthma, chronic pulmonary obstructive

disease, tuberculosis, peptic ulcer disease, inflammatory bowel disease, HIV infection

and AIDS, hepatitis, anemia, Type 1 and type 2 diabetes, cancer and its types, rheumatoid

arthritis, schizophrenia, depression, migraine, anxiety, insomnia, normal ranges of

laboratory parameters


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MODULE III: GENERAL PHARMACOLOGY & PHARMACOKINETIC &

PHARMACODYNAMIC OF DRUGS 70 hrs

• General Pharmacology-: Introduction, scope and branches of pharmacology, sources of

drugs and nomenclature of drugs, dosage forms, Routes of drugs administration and drug

delivery systems, factors modifying drug action, tolerance and dependence, dynamics of

absorption, distribution and excretion of drugs, Basic pharmacokinetic parameters

employed in the use of drugs, their bioavailability and biotransformations, metabolizing

enzymes as targets of drugs action- enzyme induction and inhibition, biological half-life

and its significance, Models of pharmacokinetics, Pharmacodynamics-mechanism of drug

action, site of drug action, drug receptor interaction types of receptors, Bioavailability

and Bioequivalence, Drug antagonism and synergism, dose response relationship, drug

dependence, Adverse drug effects and their monitoring, Iatrogenic diseases,

Pharmacogenomics and pharmacoeconomics.

• Overview of Drug Pharmacology: Current interventions, classification of drugs,

pharmacokinetics, therapeutic effects, mechanism of action, adverse effects and

contraindications, dose, marketed preparations of the following class of drugs:

� Drugs acting Central Nervous System(CNS): Autonomic and somatic transmission,

General anesthetics, anxiolytics and hypnotics drugs, anti depressants, CNS

stimulants and psychotomimetic drugs, Opioid analgesics and opioid anatagonists,

Drug dependence and drug abuse, Antiepileptic drugs, Drug therapy for

neurodegenerative disorders like parkinson’s disease and schizophrenia.

� Drugs acting on Autonomic Nervous System (ANS): General introduction,

Parasympathomimetic, parasympatholytic, Sympathomimetic, sympatholytic agents,

Ganglionic stimulants, blockers and adrenergic neuron blocking drugs, local

anesthetics

� Drugs acting on Cardiovascular System (CVS): Cardiac glycosides and positive

ionotropic agents, Anti-arrhythmic drugs, Antihypertensive drugs, Coronary


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vasodilators and drugs used in angina, Anti-hyperlipidemic drugs, Fibrinolytic agents,

Cardioprotective agents, Anti-anginal agents

� Antihypertensives: Overview, classification of antihypertensive drugs -- Diuretics,

Sympatholytics, angiotensin inhibitors, vasodilator, dopamine agonists

� Drugs acting on Respiratory System: Expectorants, Anti-tussive bronchodilators,

Drugs used in common cold

� Anti Cancer: Types of cancer, etiology of Cancer, drugs used in cancer

chemotherapy, toxicities of drugs used in cancer chemotherapy, resistance to

cytotoxic drugs, Preferred combination chemotherapy for certain malignancies

� Anti Diabetic: Insulin preparation, types of diabetes, Antidiabetic drugs:

Sulfonylurea drugs, Meglitinide drugs, Alpha-glucosidase inhibitors, Biguanide,

thiazolodinediones

� Non Steroidal Anti-Inflammatory Drugs( NSAIDS): Classification of NSAIDS,

Mechanism of action, NSAIDS which do not inhibit prostaglandin synthesis

� Anti-Coagulants, Antiplatelet and Fibrinolytic Drug : Normal hemostatis,

anticoagulant drugs, parenteral anticoagulants, antiplatelet drugs, fibrinolytic drugs

� Chemotherapy of Microbial Diseases: Introduction to chemotherapy, Sulfonamides,

Qinolones and treatments of urinary tract infection, Penicilins, cephalosporins and

other β- lactum antibiotics, Aminoglycosides, Microlides, other antibacterial drugs,

broad spectrum antibiotics: Tetracyclines and chloramphenicol, Chemotherapy of

tuberculosis and leprosy

REFERENCES FOR READING

• Elements of Human Anatomy Physiology & Health Education by Dr Ramesh

Goyal

• Elements of Pharmacology by Dr Ramesh Goyal, Dr. Anita Mehta

• Handbook of Pathophysiology by Joan P Frizzell

• Text Book of Pathophysiology by Dr. Rajpal Bansal, Dr. Anu Gupta

• Anatomy and Physiology in Health and Illness by Anne Waugh, Allison Grant


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• Human Anatomy Vol 1, Upper Limb & Thorax by B D Charuasia's

• Human Anatomy Vol 2 Lower Limb, Abdomen & Pelvis by B D Charuasia's

• Human Anatomy Vol 3, Head, Neck & Brain by B D Charuasia's

• Textbook of Physiology for Dental Students by H V Tandan , R Chandramouli

• Color Atlas of Pharmacology Ebooks by Heinz Lullmann, Kaus Mohr, Luts Hein,

Detlef Bieger

• Basic and Clinical Pharmacology by Katzung B

• Pharmacology by Brenner G

• Principles of Pharmacology by Golan D

• Principles of Pharmacology by Sharma H

• Pharmacology for the Health Care Professions Ebook by Christine M Thorp


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SEMESTER II

MODULE IV: PHARMA-MEDICINE & CLINICAL RESEARCH 70 hrs

• Drug Discovery: Drug design-Ligand based, Structure based, Active site identification,

rational drug discovery High throughput screening, Structure Activity Relationship

(SAR), Quantitative Structure Activity Relationship (QSAR), Computer assisted drug

designing (CADD)

• Phases in Clinical Development of Drug : Terminology in clinical research, Preclinical

phases, First in human trials, Single ascending dose and multiple ascending dose studies,

Exploratory clinical trials, Confirmatory clinical trials, post marketing surveillance

• Preclinical Study Guidelines : Non clinical overview and non clinical

summaries(M4S(R2)), Non clinical safety studies(M3(R1)), Guidance on non clinical

safety studies for the conduct of Human clinical trials and marketing authorization, Dose

response information to support drug registration(E4), Clinical safety data management,

guideline on the need of carcinogenicity studies of pharmaceuticals(S1A), Duration of

chronic toxicity testing in animals (rodent and non rodent toxicity testing (S4), safety

pharmacology studies for human pharmaceuticals (S7A), Non clinical evaluation for anti

cancer pharmaceuticals (S9)

• History & Background of Origin of Clinical Research: Thalidomide tragedy,

Sulphanilamide disaster, WMA Declaration of Helsinki- Ethical Principles for Medical

Research Involving Human Subjects, The Belmont Report

• Types of trials: Pharmacoepidemiology, Meta-analysis, Case control study, Prevention

Trials, diagnostic trial, Treatment trial, Case cohort study, Observational studies, Quality

of life trials

• Fundamentals of Trial Design – Randomized clinical trial, uncontrolled trials, protocol

development, end points, Patient selection, sources and control of bias, Randomization,

sample size and power

• Clinical/Contract Research Organizations(CRO) - Definition, fundamental operations

of CRO, Role and responsibilities of CRO, Organogram of CRO, basic documentation in


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CRO, Site Management Organizations (SMO), Central Lab, Research Management

Organizations and differences between Contract Research Organization/Site Management

Organization/Research Management Organization, Functions of Quality Assurance and

Quality Control Departments, Bioanalytical Departments, Clinical Project Management,

Regulatory affairs, Medical Writing and Data Management, Biostatistics, Establishment of

CRO/SMO/RMO

• Study Execution Process- Study design, Feasibility, Overview of National regulatory

applications, CR professional training and development, preparations and planning for

clinical trials, CRF and monitoring, Training and site management, Budget Management

of Clinical trials


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MODULE V: REGULATIONS IN CLINICAL RESEARCH 70 hrs

• Ethical Aspects: Ethical principals underlined research involving human subjects,

respect for persons, beneficence, justice, legal authorities for Institutional Review Board

(IRB), Heath and Human Services regulations (HHS) , FDA regulations, regulatory

requirements, duties of IRBs, IRB membership, role of IRB in reviewing Clinical Drug

Trials, Assessment of scientific design, competence of investigator, selection of subjects,

balancing benefits and risks , Compensation for research related injuries, special issues

like role of Lay member of IRB, review of multi institutional trials, duty to monitor,

financial risks of clinical trial subject, compliance with new regulations

• History of Good Clinical Practices (GCP): Introduction to ICH-International

Conference on Harmonization of technical requirements for registration of

Pharmaceuticals for human use guidelines Milestones in the evaluation of GCP , The

Nuremberg Code, Principles of ICH-GCP

• Applicable GCP Guidelines: International Conference on Harmonization of technical

requirements for registration of Pharmaceuticals for human use guidelines (ICH-GCP),

Indian Council Of Medical Research- Ethical Guidelines for Biomedical Research on

Human participants (ICMR), Indian Good Clinical Practices

• International Regulatory bodies and Guidelines:

o US Food and Drug Administration(USFDA): The FDA and Food Drug and

Cosmetics Act, New drug development and approval : the principal steps

o India: Regulatory laws, Schedule Y, Schedule Y1, registration of new drugs,

requirements for registration, regulatory environment and practices

o Medicines and Healthcare Products Regulatory Agency (MHRA): Overview of

regulatory environment/ background, regulatory authorities, regulatory requirements

and procedures

o European Agency for Evaluation of medicinal Products(EMEA): National

registration , the decentralized procedures, mutual recognition procedures

o Brazil: Overview of regulatory affairs


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o Good Laboratory practices(GLP) : Organization and Personnel, Quality assurance

program, Facilities, Equipments, reagents and Materials, Standard operating

procedures, Storage of Records and Reports

• Council for International Organizations of Medical Science (CIOMS) guidelines:

CIOMS International Ethical guidelines for biomedical research involving human

subjects, Principles Of Medical Ethics Relevant To The Protection Of Prisoners Against

Torture (1983)

• Intellectual Property Rights: Terminology, Patent Laws, TRIPS (Trade Related

Intellectual Property Rights) Agreement, Trademarks, copyrights

• Clinical Trial Application Requirements

o Investigational New drug (IND): Classifications, IND application submission

check list, FDA IND review check list , IND application process, Information for

sponsors-investigator submitting IND, IND forms and instructions

o New Drug Application(NDA): Pre NDA meeting , NDA submission Check list ,

FDA NDA review check list

o Abbreviated New drug Application(ANDA): ANDA content, ANDA

Submission check list , FDA ANDA review check list , ANDA process for

generic drugs, guidance documents for ANDAs, ANDA forms and electronic

submissions

o Orphan Drugs Application : Submission check list, FDA orphan drug review

check list , FDA documents


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MODULE VI: CLINICAL RESEARCH OPERATIONS MANAGEMENT 70 hrs

• Operation in CRO & SMO

o Site Selection Criteria- Site Selection parameters: Location, Staffing,

Qualifications, History, Clinical trial experience, Area of therapeutic experience,

Investigational pharmacy, ICH-GCP compliance, Patient enrollment, Site

Selection Check list, Site Initiation Visit (SIV)

o Single Centre/Multi Centre Trial - Definition, benefits of Single centre and or

Multi centre, Differences between Single centre & Multi centre Trial

o Investigator Selection

Investigator qualification and agreement, duties delegation, Undertaking by the

Investigator, Feasibility study, Other functions-Central lab, Shipment and

shipping records, meetings with Sponsor, analysis & interpretation of results etc

• Operation of Institutional Review Board (IRB)/ Independent Ethics Committee

(IEC) - Defining Scope of IRB/IEC Authority, Responsibilities of IRB/IEC, Composition

of IRB/IEC, Basic Functions, Operation and Procedure of IRB/IEC, Communication with

IRB, IRB/IEC Records, Documents for submission to IRB/IEC, Difference between IRB

and IEC

• Roles & Responsibilities of Clinical Trial Personnel

o Roles & Responsibilities of Sponsor

o Roles & Responsibilities of Investigator

o Roles & Responsibilities of CROs/SMOs

o Roles & Responsibilities of CRA/Monitor

o Roles & Responsibilities of Auditor

o Roles & Responsibilities of Clinical Research Coordinator

o Roles & Responsibilities of Clinical Data Manager

o Roles & Responsibilities of Clinical Biostatistician


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• Clinical Trial Documentation:

o Investigator’s Brochure- Confidentiality Statement, Summary, Introduction, Physical,

Chemical, and Pharmaceutical Properties and Formulation, Nonclinical Studies,

Nonclinical Pharmacology, Pharmacokinetics and Product Metabolism in Animals,

Toxicology, Effects in Humans, Pharmacokinetics and Product Metabolism in Humans,

Safety and Efficacy, Marketing Experience, Summary of Data and Guidance for the

Investigator

o Study Protocol - The contents of a trial protocol should generally include the topics:

General Information, Background Information, Trial Objectives and Purpose. Trial

Design, Selection and Withdrawal of Subjects, Treatment of Subjects, Assessment of

Efficacy, Assessment of Safety, Biostatistics, Direct Access to Source Data/Documents,

Quality Control and Quality Assurance, Ethics, Data Handling and Record Keeping,

Financing and Insurance, Publication Policy, Supplements, Annexure

o Case Report Forms (CRF) & e-CRF- Study Title, Inclusion Criteria, Exclusion

Criteria, Patient Screening, Admission /discharge procedure, Visit wise, Period wise,

Laboratory Analysis, Vital signs, Diet restriction, Concomitant medication,

withdrawal/drop out details, Adverse Events Form, Serious Adverse Event Form

o Informed Consent Form/Assent Form- Study title, What is the purpose of research,

The study design, Study Procedures, Women of childbearing potential, Possible risks ,

Possible benefits, Compensation, Possible benefits to other people, The alternatives you

have, Cost to the participant, Confidentiality of the information of subject/patient,

decision to participate/ not participate, Withdrawal of the consent, Right to new

information, Contact persons, Patient consent form, Patient Information Sheet, Patient

visit diary

o Clinical Study Report- Title Page, Synopsis, List Of Abbreviations And Definitions Of

Terms, Ethics, Investigators And Study Administrative Structure, Introduction, Study

Objectives, Investigational Plan, Study Patients, Efficacy Evaluation, Efficacy

Evaluation, Discussion And Overall Conclusions, Tables, Figures and Graphs Referred,

Reference List, Appendices


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• Standard Operating Procedures (SOP) in Clinical Trials - Need of SOPs, What is

SOPs, Benefits of SOPs, different types of SOPs, SOP Writing SOPs and Guideline,

Implementation and monitoring of SOPs, Change control

• Essential Documents-Importance of Essential Documents

o Pre Study Document: Investigators Brochure, Financial aspects of the trial,

Approval letter from the IRB, IRB Composition etc

o During the Study Documents: Updates on medical/laboratory/technical

procedure tests, Investigational product(s) accountability at site, Subject enrolling

log, Audit certificate etc

o Post Study Documents: Final report by investigator to IRB, Final report by

investigator to regulatory authorities, Clinical study report to document results

and interpretation etc, Study Completion documents, Study Termination/closure

documents

• Procedures in Clinical Trial

o Quality Assurance and Quality Control in Clinical Research –Introduction,

Regulatory requirement of quality Assurance(QA) and Quality Control (QC) in

Clinical Research, Role and Responsibilities of QA personnel, Different types of

Audit, Quality System and Quality Policy, Continual Process Improvement

o Interventions, Study Drug Packaging and Distribution Study Drug Receipt,

Dispensing, Accountability, Storage, Disposal, Regulatory Requirement. An over

view of clinical trial interventions, describe issues related to study drug packaging

and masking, discuss logistics of study drug distribution, and describe treatment

adherence in clinical trial

o Monitoring in Clinical Trials : Purpose of monitoring & Monitor’s

responsibilities, Selection and qualification of monitors, Monitoring procedures,

Monitoring report, Audit, Extent and nature of monitoring , Medical Monitoring,

Query Resolution


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o Project Management and Business Development: Skills of Business

Development personnel, Roles and responsibilities of a Project manager, Project

Management matrix, Business development strategies


• Business Development for the Biotechnology and Pharmaceutical Industry by Martin

Austin

• Clinical Drug Trials & Tribulations Ebooks by James Swarbrick

• Clinical Research Coordinator Handbook Ebook by Deborah Rosenbaum, Michelle

Dresser

• Clinical Trial Medicine Ebook by Richard Chin, Bruce Y. Lee

• Clinical Studies Management by Simon Cook

• Clinical Trials – Ebooks by Duolao Wand, Ameet Bakhai Remedica

• Good Clinical Practice by Josef Kolman, Paul Meng

• Guideline for Drug Regulatory Submissions by Sandy Welnberg

• International Pharmaceutical Registration by Alan A Chalmers

• International Research in Health Care by Felicity Smith, Sally Anne Francis, Ellen

Schathecutle

• Quality Management in Clinical Trial Research Ebook by Graham D. Ogg

• Pharmaceutical Biotechnology by O Kayser, R H Muller

PRACTICAL EXERCISES & EXPOSURE

• Case studies solutions

• Technical and soft skill presentations

• Term search

• Development of Clinical research documents

o SOPs development

o CRFs & ICFs Preparation


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o Dummy clinical research and bioequivalence protocols etc,

• Role plays of real clinical research stake holders like Clinical research associate,

investigator, project manager, volunteer, clinical research coordinator, auditor etc

INDUSTRIAL EXPOSURE

During initial visit an overview of the facility infrastructure, flow of activity, visiting

different areas like screening room, medical examination room, phlebotomy room, dining

area, baggage and body area, clinical pharmacological unit, dosing area, investigator`s cabin,

drug store, plasma separation and storage room.

On site exposure which includes observation of actual in-process activities like blood

collection, plasma separation, screening of volunteers, informed consent process.

A visit to Analytical Department and Central Laboratory to have know-how of the

tests/investigations conducted and other procedures performed in respective departments


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SEMESTER III

MODULE VII: CONDUCT OF BIOEQUIVALENCE STUDIES 70 hrs

• Introduction to Bioavailability & Bioequivalence- Basic Definitions, Requirements of

Bioavailability and Bioequivalence study, Study Design, Bio statistical procedure, Bio

analytical method and Method validation, submission of study to the regulatory,

Bioequivalence and Pharmacokinetics

• Guidelines of Bioavailability (BA)/ Bioequivalence(BE) Studies

o USFDA guideline- Introduction, Background, Methods to document BA and BE,

Comparison of BA measures in BE studies, Documentation of BA and BE, Special

topics, General pharmacokinetic study design and data handling

o ANVISA guideline- Introduction, Background, Acceptance Criteria of BA/BE Unit,

General Consideration for BA/BE study, Guidance for Protocol Design of BA/BE

study, Guidance for report preparation of BA/BE study

o Overview of International BABE guidelines: Therapeutic Goods Administration

(TGA) guideline, Therapeutic Product Directorate (TPD) guideline, European

Agency for Evaluation of medicinal Products (EMEA) guideline

• Regulatory Submissions: Drugs Controller General of India (DCGI)/Central Drugs

Standard Control Organization (CDSCO) submissions, Directorate General of Foreign

Trade (DGFT), T-License, e-CTD (Common Technical Document)

• Difference in various Bioavailability (BA)/ Bioequivalence (BE) Guidelines- Different

Regulatory Bodies and differences in terms of: Selection of Reference Product, Drug

content / potency, Number of subjects, Inclusion Criteria, Exclusion Criteria, Dosing

Water Quantity. Water restriction and food restriction, requirement of Fed Study,

Minimum sample points, Length of blood sampling time, Washout, Metabolites

concentration measurement, Drugs with non-linear Pharmacokinetic, Drugs with Long

Half-life, Modifies release formulation, Withdrawal /dropout criteria, Outliers, Retention

period for Study Drugs sample


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• Conduct of Bioequivalence study- Role of Different Departments involve in

Bioequivalence study (Business development, Screening department, Clinical

department, Bio-analytical department etc), Life span of Bioavailability and

Bioequivalence study(BABE study), day to day activity during the study

• Operations in BABE: Role of Quality Assurance & Quality Control in BA/BE studies,

Role of Medical Writing in BA/BE studies, Waiver of BA/BE Studies, Role of Project

Management and Business development in BA/BE studies


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MODULE VIII: CLINICAL DATA MANAGEMENT & BIOSTATISTI CS 70 hrs

• Introduction to Clinical Data Management(CDM): Definition, Steps in CDM, Data

management process and work flow, Code of Ethics for CDM professionals , CDM and

case record form (CRF), needs of CRF users, standardization of CRFs, guidelines for

designing CRF, CDISC

o Data Entry/Remote data entry: First data entry, Second data entry, heads up and

heads down data entry, audit trail, 21CFR part 11, computerized system in clinical

trials, QAQC in data entry

o Data Tracking: Tracking CRF pages and corrections, CRF work flow, tracking

challenges, tracking of query forms

o Data Capture: Definition, paper based and electronic data capture, dataflow in

paper CRFs and e-CRFs, tools for data capture, advantages and disadvantages of

paper CRF/ e-CRF

o Data Coding: Definition, data quality, coding significance, coding dictionaries,

Coding symbols for a thesaurus of adverse reaction terms (COSTART), problems

with Coding data, special search categories, coding of AE data

o Data cleaning/validation: Definition, Discrepancy management system, edit check

specifications, query management, cleaning data checklist, SAE reconciliation,

managing laboratory data, data locking/freezing

o Overview of Data management Software(s)

• Introduction to Biostatistics & its role in Clinica l Research: Population & Sample,

Parameter & Statistic, Types of variables, Measures of Central Tendency-Mean, different

types of mean, Median, Mode, Histograms, Scatter Plots, Construction & Labeling of

graphs, Normal & Binomial Distribution, Research Hypothesis testing, Sample size

calculation & Power, p-value, Confidence Interval, Randomization methods, Blinding in

Clinical research


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• Parametric tests & Non-parametric tests and its applications: t-test, Z-test, chi-square

test, ANOVA, ANCOVA, Spearman’s correlation coefficient test, Wilcoxon Rank Sum

Test, Kruskal-Wallis test, Rank correlation, linear regression & correlation


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MODULE IX: PHARMACOVIGILANCE & POST MARKETING SURVE ILLANCE

70 hrs

• General overview of Pharmacovigilance: Introduction, Definitions, Adverse Event

(AE), Adverse Drug Reaction(ADR), Serious Adverse Drug Reaction (SAE), Unexpected

Adverse Reaction, Suspected-unexpected serious Adverse reaction (SUSAR), Signal and

Detection of Signal, Diagnosis and management of adverse drug reactions, Periodic

safety Update Report(PSUR), Individual case safety report, Spontaneous reporting, Risk

Evaluation and Mitigation Strategy, Significance of Pharmacovigilance, Audit in

Pharmacovigilance

• Pharmacovigilance and ICH guideline: ICH-E2A Clinical Safety Data Management –

Definitions and Standards for Expedited Reporting, ICH-E2CR1 Clinical Safety Data

Management – Periodic Safety Update Reports for Marketed Drugs, ICH-E2CR2-

Periodic Benefit-Risk Evaluation Report, ICH-E2D Post-Approval Safety Management –

Definitions and Standards for Expedited Reporting, ICH-E2E Pharmacovigilance

Planning

• Pharmacovigilance regulations and guidelines: Role of Pharmacovigilance in Drug

Regulation, Regulatory aspects in Pharmacovigilance, European Union PV guidelines,

Australian PV guidelines, Good Pharmacovigilance practices (GPP), Expedited reporting

requirements

• Pharmacovigilance in India: Pharmacovigilance centers in India, CDSCO Indian PV

guidelines-National Pharmacovigilance Program (NPP)

• Pharmacovigilance in Europe: Guidelines for Marketing Authorization Holders

(MAH), General Principles, Risk management plan(RMP), Contents of EU-RMP,

Expedited Reports, Reporting in Special Situations, Periodic Safety Update Report

(PSUR)


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• Adverse Event reporting form: MEDWATCH, CDSCO Adverse Event Reporting

Form, CIOMS form for Serious Adverse event reporting, Anonymised Single Patient

reports (ASPR-MHRA), Medication errors reporting

• Pharmacovigilance Dictionaries: MedDRA (Medical Dictionary for Regulatory

Activities), MedDRA structure and content, WHOART (WHO-Adverse Reaction

Terminology), Eudravigilance, CO-START

• Global Pharmacovigilance & safety standards- Pharmacovigilance activity in USA,

Australia, WHO Monitoring of safety aspects – Uppasla Monitoring Center

• Periodic safety update reports(PSUR) for marketed drugs : Brief Introduction and

Purpose of Periodic safety Update Report, PSUR Content, PSUR Process, Various

Regulatory Requirement for PSUR


• A Handbook of Bioanalysis and Drug Metabolism by Gary Evans

• Biostatistics: The Bare Essentials by Norman G

• Clinical trial risk management by Martin Robinson & Simon Cook

• Clinical Trials: A Practical Guide to Design, Analysis & Reporting by Duolao Wang &

Ameet Bakhai

• Data Monitoring committees in Clinical Trials Ebook by Susan S Ellenberg, Thomas R

Flemming, David L Demets

• Drug Safety Evaluation by Shayne C Gad

• Guideline for Drug Regulatory Submissions by Sandy Weiberg

• Handbook of Bioequivalence testing by Sarfaraz K. Niazi

• Introduction to Statistics in Pharmaceutical Clinical Trials by Todd A Durham & J Rick

Turner

• Phramaceutical statistics; Practical and Clinical Application by Sanford Bolton

• Practical Guide to - Clinical Data Management by Sisanne Prouscha

• The Design for studies for Medical Research by David Machin & Michael Campbell


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PRACTICAL EXERCISES & EXPOSURE

• Case studies solutions

• Technical and soft skill presentations

• Term search

• Development of Clinical research documents

o SOPs development

o CRFs & ICFs Preparation

o Dummy clinical research and bioequivalence protocols etc,

• Role plays of real clinical research stake holders like Clinical research associate,

investigator, project manager, volunteer, clinical research coordinator, auditor etc

• Technical article discussions

• Open book exam

• Mock exams

• Group Discussions

INDUSTRIAL EXPOSURE

During initial visit an overview of the facility infrastructure, flow of activity, visiting different

areas like screening room, medical examination room, phlebotomy room, dining area, baggage

and body area, clinical pharmacological unit, dosing area, investigator`s cabin, drug store,

plasma separation and storage room.

On site exposure which includes observation of actual in-process activities like blood collection,

plasma separation, screening of volunteers, informed consent process.


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A visit to Analytical Department and Central Laboratory to have know-how of the

tests/investigations conducted and other procedures performed in respective departments


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SEMESTER IV

DISSERTATION

• This crucial part of course gives you the chance to apply the research skills acquired

during the taught phase of course to a practical problem in clinical research. The

project can be undertaken in a variety of settings including academia or industry.

• This is a fantastic opportunity to apply your new found knowledge and skills in a real

life setting; it also allows you to make invaluable contacts with potential employers

before even completing the program. Also, working in a team, using knowledge and

skills gained during the taught modules you will prepare a substantial platform for

yourself to carry out diverse documentation activities at your end

• The marks are obtained from a combination of a submitted dissertation, oral presentation of

your research and applications and initiative shown during the project